In the fourth year, the in vivo efficacy of CHD-FA to treat cutaneous and burn wounds infected with multidrug resistant Gram-negative bacteria P. aeruginosa or Gram-positive bacteria MRSA was evaluated. In these trials, histopathological analyses and wound healing gene expression profiling demonstrated alleviated inflammation and promoted healing upon CHD-FA treatment. The bacterial burden assessment also found a significant burden reduction from wounds treated with CHD-FA. In both cutaneous and burn model of the 6-day P. aeruginosa study, bacteria were completely eliminated from infected wounds as rapidly as 24h post-inoculation with twice daily application of CHD-FA. Similarly, promising in vivo antimicrobial efficacy was also observed in the cutaneous and burn wound model with MRSA. However, the microbial burden restored from day 3 till day 6 in the cutaneous wound infection model. Although we have previously confirmed the broad-spectrum activity of CHD-FA in vitro, CHD-FA may be less active against Gram-positive pathogens in vivo. The exact molecular mechanisms of the antibiotic activity of CHD-FA are still not clear, and will be further investigated to address the discrepancy in its activity against Gram-positive and Gram-negative pathogens in our future work. By far, CHD-FA with the modified application method enhanced absorption of drugs through the eschar and is the most promising combination to control the infection caused by rapidly growing bacterial species. Overall, we have made significant progress in the fourth year in demonstrating the value of CHD-FA to treat wound infections. We believe that the CHD-FA combined with the modified application method will be effective in treating wounds infected with major multi drug resistant pathogens and demonstrate its universality for preventing wound infections and promote healing.